title: Glucocorticoid-induced p11 over-expression and chromatin remodeling: a novel molecular mechanism of traumatic stress?
abstract: While the actions of glucocorticoids on brain function have been comprehensively studied, understanding of the underlying genomic mechanisms is advancing slowly. Recently, it was found that p11 is associated with traumatic stress and depression, and glucocorticoids regulate expression of the p11 gene. The ligand-activated glucocorticoid receptor (GR) interacts with two glucocorticoid response elements (GREs) in the p11 promoter region to up-regulate the p11 gene. RU486, a glucocorticoid receptor antagonist, and mutation of GREs both block glucocorticoid-induced p11 over-expression, suggesting that glucocorticoid-induced p11 over-expression is mediated by GR and GREs. Thus, the p11 gene can be transcriptionally activated. There is evidence that this transcriptional activation is mediated by the remodeling of chromatin complexes in response to glucocorticoid receptor-regulated promotors. The regulation of eukaryotic gene expression by chromatin remodeling is complex and is essential for numerous cellular processes. The association of linker-histone, non-histone and heterochromatin-specific proteins plays a key role in the generation of higher-order chromatin structures. Understanding the chromatin remodeling involved in the glucocorticoid-mediated increase of p11 expression by stress may clarify stress-induced over-expression of p11 and also identify a new therapeutic target for post-traumatic disorder and depressive disorders, i.e., chromatin remodeling.
authors.affiliation: Center for Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA. Lezhang@USUHS.mil
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: He
authors.initials: H
authors.lastname: Li
authors.forename: Xianzhang
authors.initials: X
authors.lastname: Hu
authors.forename: Xiao Xia
authors.initials: XX
authors.lastname: Li
authors.forename: Stanley
authors.initials: S
authors.lastname: Smerin
authors.forename: Robert
authors.initials: R
authors.lastname: Ursano
mesh_terms: D017306:Annexin A2 / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D009418:S100 Proteins / Q000235:genetics*; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics*; D000099248:S100 Calcium Binding Protein A10
chemical_list: D017306:Annexin A2; D005938:Glucocorticoids; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10